The long-term objective of the proposed research is to determine the factors involved in the packing and regulation of the genetic material in the male nucleus during spermiogenesis and fertilization in mammals. The results of cytochemical, autoradiographic, and fine structural studies of nuclei in differentiating spermatids and in the fertilizing spermatozoon of the rabbit will be correlated. By this approach, it should be possible to determine the relationships among basic protein replacements, nonhistone protein changes, oxidation and reduction of sulfur-containing amino acids, changes in chromatin packing and fine structure, and nuclear synthetic activity during mammalian spermiogenesis and fertilization. In addition, experiments are proposed to determine the characteristics of cytoplasmic factors involved in DNA template release in the fertilizing spermatozoon, utilizing an in vitro system containing isolated rabbit sperm nuclei. Although unproven, it is assumed that changes in the packing and regulation of the genetic material have great importance for the information and survival of male gametes, and for normal embryonic development. It is expected that the proposed research also will have significance for understanding certain types of male sterility.